Journal article
Hypermutation In Pancreatic Cancer
JL Humphris, AM Patch, K Nones, PJ Bailey, AL Johns, S McKay, DK Chang, DK Miller, M Pajic, KS Kassahn, MCJ Quinn, TJC Bruxner, AN Christ, I Harliwong, S Idrisoglu, S Manning, C Nourse, E Nourbakhsh, A Stone, PJ Wilson Show all
Gastroenterology | W B SAUNDERS CO-ELSEVIER INC | Published : 2017
Abstract
© 2017 AGA Institute Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design fo..
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Grants
Awarded by European Commission
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (NHMRC 631701, 535903, 427601, 1112113), Queensland Government (National and International Research Alliances Program) University of Queensland, Institute for Molecular Bioscience, Australian Government: Department of Innovation, Industry, Science and Research, Australian Cancer Research Foundation, Cancer Council NSW (SRP06-01, SRP11-01. ICGC), Cancer Institute NSW (10/ECF/2-26; 06/ECF/1-24; 09/CDF/2-40; 07/CDF/1-03; 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26,10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26, 13ECF1-46, 13/CDF/1-01), Garvan Institute of Medical Research, Avner Nahmani Pancreatic Cancer Foundation Cancer, Australia 1065022 Project Grant funding, R.T. Hall Trust Petre Foundation, Jane Hemstritch in memory of Philip Hemstritch Gastroenterological Society of Australia, American Association for Cancer Research, Landon Foundation - INNOVATOR Award, Royal Australasian College of Surgeons, Royal Australasian College of Physicians, Royal College of Pathologists of Australasia, Queensland Institute of Medical Research, Berghofer Medical Research Institute, Keith Boden Fellowship, Italian Ministry of Research (Cancer Genome Project FIRB RBAP10AHJB), Associazione Italiana Ricerca Cancro (12182), Fondazione Italiana Malattie Pancreas - Ministero Salute (CUP_J33G13000210001), European Community Grant FP7 Cam-Pac Cam-Pac, Grant agreement no: 602783, National Institutes of Health grant CA62924. Cancer Research UK, Wellcome Trust, Pancreatic Cancer UK, Howat Foundation.